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Cell Cycle. 2007 May 15;6(10):1249-56. Epub 2007 May 1.

Cell cycle regulation targets of MYCN identified by gene expression microarrays.

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  • 1Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.



We have previously shown that MYCN knockdown causes a G1 arrest in MYCN amplified (MNA), p53 wild type (wt) and p53 mutant MNA neuroblastoma cell lines, with increases in p21(WAF1) and hypo RB in p53 wt cell lines.


MYCN acts by inhibiting p21(WAF1), and also by p21(WAF1) independent mechanisms to override the G1 checkpoint in exponentially growing cells.


Genes potentially regulated by MYCN were identified using gene expression microarrays in p53 wt MNA IMR-32 and p53 mutant MNA SKNBE(2c) neuroblastoma cell lines treated with MYCN or scrambled siRNA. Results were validated using qRT-PCR and confirmed using the regulatable MYCN expression system (SHEP Tet21N).


MYCN knockdown altered the expression of several cell cycle related genes. SKP2 was down regulated in both cell lines, and up regulated in MYCN+ Tet21N cells. Expression of the WNT antagonist DKK3 increased in both cell lines and decreased in MYCN+ Tet21N cells. Expression of CDKN1C (p57(cip2)) and TP53INP1 also increased after MYCN knockdown.


MYCN may override the G1 checkpoint through down-regulation of SKP2 and TP53INP1 resulting in reduced p21(WAF1) expression in p53 wt cell lines, and in addition may act through the WNT signaling pathway in a p53 independent manner.

[PubMed - indexed for MEDLINE]
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